Recently in Neuropsychiatry Category
In the current housing market, a seller's serotonin levels may determine just how likely a buyer's low offer will be accepted. Serotonin depletion and the acceptance of unfair offers were recently explored on a smaller scale by researchers at the University of Cambridge and UCLA by using the so-called Ultimatum Game—a game which uncomfortably resembles today's property transactions.
The investigators examined the responses of 20 healthy volunteers, who underwent a double-blind, placebo-controlled depletion of tryptophan,* the amino-acid precursor of serotonin. After the procedure, participants were offered 1 of 3 ways to split a sum of money with another player: fair (45% of stake); unfair (30%); or most unfair (20%).
The investigators found that respondents were significantly more likely to reject "most unfair" offers after tryptophan depletion than after placebo treatment (F = 7.551; P = .013). However, the rejection rates of fair or unfair offers were not significantly affected by tryptophan depletion. On the basis of related assessments, the researchers concluded that the higher rejection of "most unfair" offers with tryptophan depletion could not be attributed to other factors, like changes in mood.
* Acute (5-hour) tryptophan depletion results from the ingestion of a tryptophan-free amino-acid drink (see Young SN et al. Psychopharmacology (Berl). 1985;87:173-177).
Photo: iStockPhoto
By now, pretty much everyone has seen the June 19 videotape of Esmin Green, 49, dying on the waiting room floor of Brooklyn's Kings County psychiatric facility, aka G Building, while others―including security guards―saw the prostrate woman and did nothing. Until it was too late.
But reports of inhumane psychiatric care at Kings County Hospital (dubbed "Killer County" by online wags) are nothing new. A search of the NYT archives reveals that repeated and gross deficiencies in treatment existed there at least as far back as the 1960s. On a least 2 occasions, the facility lost its accreditation status, according to the paper. The remarkably dubious history of the public facility, culminating in Green's death, suggests that blame could go as high up as possible, arguably to city hall.
Last year, the Mental Hygiene Legal Service (MHLS) and the NY Civil Liberties Union, on behalf of patients, filed suit against the NYC Health and Hospital Corporation (HHC) and others, alleging that the Kings County facility is a "chamber of filth, decay, indifference, and danger where individuals...are subjected to overcrowded and squalid conditions often accompanied by physical abuse and punitive injections of mind-altering drugs." The plaintiffs cite lack of basic sanitation and laundry services, inadequate food, no wheelchair accessibility, vermin infestation, and neglect alternating with verbal or physical abuse from healthcare staff and security personnel.
The HHC, the largest city hospital and healthcare system in the United States, comprises more than a dozen hospitals, including Kings County, in the city's 5 boroughs. The HHC Chairperson, Charlynn Goins, along with HHC President and CEO, Alan D. Aviles, are named defendants in the lawsuit. Goins and Aviles, both lawyers, were appointed to their positions by Mayor Bloomberg in 2004 and 2005, respectively. Yesterday, Aviles provided a written statement to new sources on the death of Green: "We are shocked and distressed by this situation. It is clear that some of our employees failed to act based on our compassionate standards of care."
The suit also names the following defendants, at least 2 of whom are longstanding employees of Kings County:
- Jean G. Leon, RN, Executive Director, Kings County Hospital: Leon, a native of Trinidad, has evidently held her position for at least 13 years (see 2005's "10 years of inspired leadership"). A PR-type video on YouTube featuring Leon was posted April 2008.
- Kathie T. Rones, MD, MPH, Medical Director, Kings County Hospital: Rones, a 1980 graduate of the Brown University School of Medicine and a board-certified internist, has held her position since 1996. She received a tribute for her services from the NY House of Representatives on April 3, 2006.
- David K. Dailey, MD, Chief of Psychiatry, Kings County Hospital: According to the NY State Department of Health, Dailey is a 1981 graduate of the Loyola University Chicago, Stritch School of Medicine and has been licensed in the state since 1998.
- Joseph A. Charlot, MD, Comprehensive Psychiatric Emergency Program, Kings County Hospital: Charlot received his medical degree in 1968 from the State University of Haiti and has had a NY medical license since 1979.
- Ellen B. Tabor, MD, Medical Director, Adult Psychiatric Inpatient Services, Kings County Hospital: Tabor is a 1983 graduate of the Rush University School of Medicine in Chicago. She has held a NY medical license since 1990.
- Jacqueline Purser, Captain, Hospital Police
- Oswald David (or David Oswald), Assistant Director of Nursing/Product Line Manager, Comprehensive Psychiatric Emergency Program, Kings County Hospital
- Elsa P. Bush, Associate Executive Director of Nursing, Kings County Hospital
According to today's NYT, the hospital fired the director of psychiatry, the doctor on duty, and the director of security at Kings County on June 20, the day after Green died. It is not clear if the "director of psychiatry" refers to Dailey, Charlot, Tabor, or someone else. According to Esmin Green's medical records, provided by the NYCLU, a "Dr. Estes" was on duty at the time of her death. Two nurses and one security guard were also "suspended pending union-mandated hearings."
The NY Daily News provides earlier coverage and more background on Esmin Green and Kings County:
June 27 "Shocking death on Kings County Hospital psych ward stirs reform call"
June 22 "Video shows staff ignored patient later found dead"
June 21 "Patient dies waiting for bed at Kings County Hospital"
June 21 "Video shows Brooklyn hospital staff ignore patient later found dead"
May 17 "US Attorney probes claims of patient abuse at Brooklyn psych ward"
In addition to a Federal investigation of civil rights violations at Kings County, the latest reports indicate that criminal charges are being considered in the case of Green's death.
07/03/08 update: The NY Daily News reports that Pierre R. Arty, MD, the head of psychiatry at Kings County, was 1 of 6 people fired after Esmin Green's death. The others included Kenneth Jones, the hospital's director of security, and the 2 security guards (not 1, as previously reported) seen in the waiting-room videotape.
While the FDA considers whether to add suicide warnings to the labels of 11 epilepsy drugs,* the measure is unlikely to affect prescriptions—at least by neurologists. That's because the cost of nonadherence to anticonvulsant therapy among epileptic patients is known to be so high.
For example, in this week's print issue of Neurology, investigators report a 3-fold increased risk of death among nonadherent epileptic patients in a retrospective study of Medicaid claims from Florida, Iowa, and New Jersey (N = 33,658).** Nonadherence, determined by non-possession of medication, was also associated with significantly more ER visits (50% increased risk), hospital admissions (86%), car accidents (108%), and bone fractures (21%).
In the FDA's assessment of 199 placebo-controlled studies of patients with epilepsy, selected psychiatric illnesses, or pain conditions (N = 43,892), there were only 4 (0.009%) suicides in drug-treated patients and none in placebo-treated individuals. Suicidal behavior or ideation was reported in 0.37% of patients who received an anticonvulsant and in 0.22% of those who received placebo. While the risk of suicidality is almost 70% higher with anticonvulsant treatment, the absolute risk remains small at 0.15%. Not surprising, the risk of suicidality with either drug treatment or placebo was lower in epileptic patients than in psychiatric patients (see table).
|
Indication |
Suicidality Risk, % |
Relative Risk Increase, % |
Absolute Risk Increase, % | |
|
Placebo |
Drug | |||
|
Epilepsy |
0.10 |
0.34 |
240 |
0.24 |
|
Psychiatric |
0.57 |
0.85 |
49 |
0.28 |
|
Other |
0.10 |
0.18 |
80 |
0.08 |
|
Total |
0.22 |
0.37 |
68 |
0.15 |
The FDA is holding a public advisory meeting on the risk of suicide with anticonvulsant drugs on July 10.
Photo: iStockPhoto.
*The 11 drugs are carbamazepine (Carbatrol; Shire); felbamate (Felbatol; Meda); gabapentin (Neurontin; Pfizer), lamotrigine (Lamictal; GSK); levetiracetam (Keppra; UCB); oxcarbazepine (Trileptal; Novartis); pregabaline (Lyrica; Pfizer); tiagabine (Gabitril; Cephalon); topiramate (Topamax; Ortho-McNeil); valproate (Depakote; Abbott); and zonisamide (Zonegran; Eisai).
**The study was sponsored by GSK, maker of Lamictal (lamotrigine). One of the study authors is an employee of GSK, and the other authors report support from GSK, in the form of research grants and/or "other activities."
Mainstream media outlets and blogs are chattering about the news that Harvard psychiatrists Joseph Biederman, Timothy Wilens, and Thomas Spencer did not fully disclose their pharma consulting fees to the university, possibly in violation of academic and federal conflict-of-interest rules. According to the online Congressional record, Senator Chuck Grassley (Iowa-R) began an investigation last fall, which sought to determine the full extent of industry fees paid to the psychiatrists. The doctors also received NIH grants for clinical studies of commercial pharmaceuticals.
Persistent investigation by Grassley revealed that, from 2000 to 2007, Biederman and Wilens each earned more than $1.6 million from commercial sources, and that Spencer earned more than $1 million, according to the record. The majority of these fees (for services that are not specified) had not been reported to the university. The propriety, or even legality, of the physicians' reporting behavior is the subject of much online speculation. However, it remains unclear what led Grassley to investigate these physicians in the first place—among any number of possible targets.
Grassley may have been alerted to Biederman (and thereby, his Harvard colleagues) through the death of 4-year-old Rebecca Riley. As reported by "60 Minutes" in September of last year, Rebecca Riley died on December 13, 2006, at her home in Hull, Massachusetts, due to an overdose of psychiatric drugs. The drugs—Depakote (divalproex; Abbott), Seroquel (quetiapine; AstraZeneca), and clonazepam—were prescribed by Tufts psychiatrist Kayoko Kifuji for the child's bipolar disorder, which was diagnosed at the age of 2 years. Before her death, Rebecca had also been given an over-the-counter cold medication and at least one additional, unprescribed dose of clonazapam by her mother (and possibly more for a period of time before the child's death).
According to "60 Minutes," Dr. Kifuji's prescribing practices were heavily influenced by the research and views of Biederman, who was interviewed for the news show. Biederman has evidently been instrumental in the trend to apply the diagnosis of bipolar disorder, in broader terms, to very young children. And with the diagnosis goes pharmaceutical treatment in the form of some drugs that have not been systematically tested in children.
In a Boston Globe story, Kifuji's lawyer stated that the Harvard psychiatrists were "by far the leading lights in terms of providing leadership in the treatment of children who have disorders such as bipolar." The paper also wrote of the extensive financial ties between pharma and Biederman, who had "received research funding from 15 drug companies and serves as a paid speaker or adviser to seven of them," including Eli Lilly (Zyprexa [olanzapine]) and Janssen (Risperdal [risperidone]). The Congressional record also reports financial ties between Biederman and BMS (Abilify [aripiprazole]), Cephalon (Vivitrol [naltraxone]), GSK, JNJ, and Pfizer.
Right or wrong, Biederman and his colleagues Wilens and Spencer have evidently influenced the diagnosis and treatment of bipolar disorder, as well as those of ADHD, through the medical literature (for example: Frazier JA et al. J Child Adolesc Psychopharmacol. 2001;11:239-250; Wilens TA et al. J Child Adolesc Psychopharmacol. 2003;13:495-505) and through pharma-supported CME programs (for example: "The Evolving Face of ADHD" and "Focus on ADHD"). The question is whether commercial funding influenced Biederman et al to promote the relatively aggressive, unapproved use of pharmaceuticals in children with psychiatric problems. The chief of psychiatry at MGH, Jerrold Rosenbaum, wrote in an e-mail to the Boston Globe, "I think a pharma person would not dare to tell Joe [Biederman] what to say...For Joe, it is his ideas and mission that drive him, not the fees."
As far as the aftermath of Rebecca Riley's death is concerned, the child's parents, Carolyn and Michael, were charged with first-degree murder and await trial. Dr. Kifuji agreed to suspend her medical practice pending an investigation by the Massachusetts medical board.
Photo: iStockPhoto.
Moving through the Web at warp speed.
As Jason Linkins at the Huffington Post indicates, we're probably familiar with the antidepressant's tagline only because we're taking the drug given the state of things.
A retrospective analysis reveals that 32 of 41 (78%) children with autistic spectrum disorders have defective function of oxidative-phosphorylation enzymes in their skeletal muscle. The data were presented by investigators from Medical Neurogenetics, a genetic-testing facility in Atlanta, at the annual meeting of the American Academy of Neurology on Sunday.
The lead investigator, John Shoffner, MD, told Medscape Neurology & Neurosurgery that, although patients with mitochondrial disorders commonly exhibit autistic features, it is unknown how common mitochondrial disease is in autism. The US government recently decided to award compensation to the parents of Hannah Poling, after it was concluded that a concentrated series of vaccinations aggravated an underlying mitochondrial disorder, which manifested clinically as autism.
The autistic children tested by Shoffner, aged 2-16 years, were referred because of potential indicators of mitochondrial dysfunction, such as increased lactate, pyruvate, or alanine levels. By analyzing mitochondrial-enzyme activity in biopsies of skeletal muscle, defects in representative proteins from 5 mitochondrial-enzyme complexes were found. Further investigation revealed that selected proteins involved in oxidative phosphorylation were abnormal.
Among 40 children, the mitochondrial DNA (mtDNA) sequences of 10 (25%) were found to be abnormal: 2 children demonstrated heteroplasmic mutations, and abnormalities in 8 remain under investigation. Shoffner concludes that nuclear DNA mutations are, therefore, the most likely cause of the observed mitochondrial defects.
In the ongoing proceedings of the state of Alaska v. Eli Lilly,* it was revealed that Lilly CEO-to-be John C. Lechleiter wrote a company e-mail in 2003 that encouraged the off-label promotion of Zyprexa (olanzapine) to pediatricians and child psychiatrists, according to a late-breaking report from the NYT.
Now it is not news that pharma clandestinely markets its drugs for off-label use, but for a company executive to urge off-label promotion in an e-mail is colossally stupid. Lechleiter's allegedly proposed off-label marketing strategy, according to the NYT, was to discuss the potential use of olanzapine in children (for whom the drug is not FDA approved), when reps were already promoting Strattera (atomoxetine) for attention-deficit disorder. The NYT also reports that, in the e-mail, Lechleiter encouraged the off-label promotion of olanzapine to neurologists for pain.
In a feeble shot at damage control, a Lilly spokesperson indicated that Lechleiter "was not advocating off-label promotion in his note but simply wanted the company to respond to physicians’ requests for information," wrote the NYT. Drug reps can respond to unsolicited requests from physicians for off-label information.
The Lechleiter e-mail will not be presented to jurors in the Alaska trial, because the claim seeking damages for off-label olanzapine promotion was dismissed.
In related news, former olanzapine rep Shamram Ahari testified before the Senate Aging Committee about Lilly's alleged sales practices. If this PharmedOut video is any indication, Ahari's probably a very compelling witness.
*Alaska wants Lilly to reimburse its state Medicaid costs for individuals who developed diabetes while taking olanzapine.
Somewhere between not caring enough to watch the Super Bowl ex-el-one-one and not finding the energy to pop in a DVD lies my extended viewing of “Celebrity Rehab.” A mini-marathon of VH1’s new reality show was available yesterday evening, and I watched several hours of the program like the combination TV addict and celebuwreck enabler that I am.
According to the VH1 web site, the show is “supervised” by Drew Pinsky, MD,* a board-certified internist and addiction medicine specialist (and as one episode reveals, a guy with very well-developed biceps), who prescribes on-camera addiction therapy for nine residents of a contestant resident, Jessica Sierra (“American Idol”), seem to be earning their present keep from reality-show appearances. (Generally, the length of the celebrities’ bios at the VH1 web site appears to correlate inversely with the quality of their contributions to the entertainment industry.)
The show itself, which incorporates what is now the traditional filming style of reality TV (including the creepy, white-eye, night-vision shots) is engaging and, yes (oh, the irony), addictive. A non-exploitative tone is set by Pinsky, who appears to genuinely care about his patients’ recovery and avoids coming across as just another celebrity-enamored physician. Thanks to Pinsky, you could actually get sucked into the idea that the program provides a realistic view of substance-abuse rehabilitation, until you remember the cameras.
And the cameras are the big objection to the show and to Pinsky’s therapy, which seems likely to fail as long as dramatic fucked-up-ness gets camera attention above and beyond sober, chain-smoking behavior. Celebrities, being first-class cravers of attention, would seem particularly vulnerable to the pull of the camera at the expense of their own substance-abuse recovery. And the more marginal the celebrity, the more desperate the craving. Case in point is the performance of Jeff Conaway, who comes off like a big, saggy, largely incoherent infant in a wheelchair. You can’t help but wonder if Conaway’s pained, over-the-top helplessness† would be just a little subtler if he knew he wasn’t being filmed. Indeed, a glimpse of the actor’s tendency to chronically pander to the camera is inadvertently revealed when Conaway, momentarily out of rehab character, jumps up in a fit of pique from his group-therapy chair, after Baldwin accuses him of bringing drugs into the facility. Ambulatory recoveries like that are rarely seen outside of televangelist performances.
But at least in Conaway's case, it does appear that he, in fact, has an active substance-abuse problem (namely alcohol and prescription opiates). In the case of other celebrities, it’s not entirely clear why they’re even in the facility. After watching several episodes, I still don’t know what Chyna’s hooked on other than the camera lens. And
Nevertheless, you think something from
Thursday’s episode is promised to provide additional details. And sadly, I’ll probably be watching—that is, if a family member doesn’t successfully flush my remote down the toilet.
*Pinsky may be best known for his longtime cohosting of the radio and MTV relationship-advice show “Loveline.”
† It’s cruel to say (write) it, but I will: Conaway was never that good of a dramatic actor.
As the statin pendulum continues to swing from the good-for-what-ails-you to the good-for-nothing position (read the latest statin criticism here, as picked up by the WSJ Health Blog here), it received an even greater push in the negative direction from a dementia study in this week’s online issue of Neurology. In the 12-year curiously titled Religious Orders Study, an ongoing prospective cross-country study of dementia in more than 900 older Catholic nuns, priests, or brothers, investigators found no association between statin use and cognitive abilities or most Alzheimer’s- or stroke-related postmortem brain findings.
Like results from other longitudinal studies, these data suggest that statins provide no protective benefit against the dementing illness. Stratification of the data indicated that Alzheimer’s disease was just as likely to be associated with more lipophilic statins (meaning statins more likely to cross the blood-brain barrier) as less lipophilic statins. Among those patients who died, statin users were significantly less likely to exhibit clinical dementia at the time of death; however, an acknowledged weakness of the study was the limited statistical power to detect a less-than-robust association between statin use and Alzheimer’s pathology, owing to relatively few statin users among those who died.*
*Statin users in study population = 119 (12.8%); statin users among deceased = 47 (17.9%).
